Structural characterization of a neutralizing mAb H16.001, a potent candidate for a common potency assay for various HPV16 VLPs

Weijin Huang; Maozhou He; Tingting Ning; Jianhui Nie; Feng Zhang; Qingbing Zheng; Rui Zhang; Ying Xu; Ying Gu; Shaowei Li; Youchun Wang

doi:10.1038/s41541-020-00236-w

Structural characterization of a neutralizing mAb H16.001, a potent candidate for a common potency assay for various HPV16 VLPs

NPJ Vaccines. 2020 Sep 23:5:89. doi: 10.1038/s41541-020-00236-w. eCollection 2020.

Authors

Weijin Huang^#¹, Maozhou He^#², Tingting Ning^#³, Jianhui Nie¹, Feng Zhang⁴, Qingbing Zheng², Rui Zhang⁵, Ying Xu¹, Ying Gu², Shaowei Li², Youchun Wang¹

Affiliations

¹ Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC), No.31 Huatuo Street, Daxing District, 102629 Beijing, China.
² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, 361102 Xiamen, China.
³ Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, China.
⁴ Division of Monoclonal Antibodies, National Institutes for Food and Drug Control (NIFDC), No.31 Huatuo Street, Daxing District, 102629 Beijing, China.
⁵ GE Healthcare Life Sciences, No.1 Tongji South Road, Yizhuang Business Development Area, 100176 Beijing, China.

^# Contributed equally.

Abstract

With more human papillomavirus (HPV) virus-like particle (VLP) vaccines to hit the market in future, a monoclonal antibody (mAb) with preferably comparable reactivity against vaccines from different expression systems and bioprocesses is urgently needed for the potency characterization. Among all mAbs against HPV16 collected, rabbit mAb H16.001 is potently neutralizing with the highest affinity, recognizes an immune-dominant epitope, and can comparably react with HPV16 vaccines from various sources. Cryo-electron microscopic (cryo-EM) structure demonstrated that 360 H16.001 Fabs could bind to HPV16 capsid in preferable binding manner without steric hindrance between neighboring Fabs, potentially supporting its identification for VLP structural integrity and utility in monitoring VLP structural probity. This structural analysis indicated that mAb H16.001 afforded unbiased potency characterization for various HPV16 vaccines and was potential for use in vaccine regulation practice. This study also showed a model process for selecting suitable mAbs for potency assays of other vaccines.

Keywords: Biotechnology; Immunology.

Grants and funding

2018ZX09101-001/Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)